Spinal degenerative disk disease (DDD) is present in the elderly of most mammalian species. The development of DDD is commonly attributed to aging in joint tissues combined with biomechanical stress over time, but the causative mechanisms are poorly understood. In normal humans, DDD first appears at about 30 years of age; it affects more than 60% of all adults by 65 years, and 100% over 85 years. It occurs in macaques, but its epidemiology and morphological features have not been described in this species, which so resembles humans in bone metabolism. This project explored the usefulness of the macaque as a biomedical model for the study of DDD. The radiographic features of the disorder are narrowing of the intervertebral spaces (the sign of degeneration of the cartilaginous disks) and bony outgrowths (osteophytes) on the vertebrae. Analysis of the spinal radiographs of 143 females aged 4.5 to 28 years showed that they experience the same degenerative changes at age s eq uivalent to humans (macaque age ( 4 _ human age). There was a clear association between increasing age and progressive degeneration of the spinal structures. Narrowing of the intervertebral spaces began at about 7 years; osteophytes were first seen at 12 years. Degenerative changes in 15-year-old macaques were similar to those seen in 60-year-old people. Weight was significantly associated with degenerative changes. Some of the oldest animals showed progression to partial ossification of the intervertebral disc. In the monkeys, DDD was concentrated in the lower thoracic area, whereas in humans DDD is more prevalent in the lumbar vertebrae. The differences between the two species probably reflect the mechanical loading associated with macaque quadrupedal locomotion vs human bipedalism. The results show that the macaque presents a potentially informative model in which to explore the factors that accelerate the onset and progression of DDD. FUNDING NIH grants RR00166 and AR40813, NSF grant SBR-93192778, and the UW Royalty Research Fund. Santoni, L., Simkin, P., Kramer, P., Ott, S., and Newell-Morris, L. Degenerative disk disease in the aging macaque. Arthritis Rhem. 41:S147, 1998 (abstract).